Impairments in physical function increase sharply with age and are significantly associated with subsequent disability. Physiologic changes during the menopausal transition related to estrogen depletion are hypothesized to lead to damage to the musculoskeletal system and subsequently to decreased function. Findings from prior observational epidemiological studies of the relationship between use of estrogens and change in functional status suggest that estrogen use may influence change in physical function. However, findings from previous studies are flawed because selection factors for estrogen use result in residual confounding. Few clinical trials have directly assessed the relation between hormone use and performance- based tests of physical function. Results from the Women's Health Initiative (WHI) randomized clinical trial are needed to define the influence of change in postmenopausal hormone use on change in physical function. Data from the WHI, including repeated performance-based measures of physical function, will allow us to consider the effects of HT (estrogen-only (E-alone), and estrogen plus progestin (E+P)) on functional limitation, and to evaluate short- and long-term changes in these measures. We will also be able to evaluate moderators of the relationship between HT and changes in physical function. The WHI data address many of the limitations of previous research, namely lack of randomized design, short follow-up period, small sample size / inadequate sample to evaluate the influence of E and E+P separately, and lack of physical performance measures (relying instead on self-reported functional limitation measures). While risks associated with HT make a change in prescription practices among postmenopausal women unlikely, a sizable number of women are still using HT in the US. In addition, many women have discontinued use of HT over the past five-years. Results from this study will be relevant to the sizable number HT users and past-users in the US and their clinicians, as well as useful for characterizing the future burden of disability in a given population. PUBLIC HEALTH RELEVANCE: Older women are at high risk of becoming disabled, making decline in physical function a critical health issue in this population. Use of estrogen may protect against declines in physical function, but the evidence is not consistent. Data from the Women's Health Initiative, a large, population-based randomized clinical trial of postmenopausal hormone therapy, will be used to define the influence of estrogen and progestin on maintenance of physical function.